1. Field of the Invention
The precise mechanisms that control the entry of viruses into the cytoplasm or nuclei are poorly understood. There is evidence that different viruses bind to unique receptor molecules on the plasma membrane of most cells. These receptors determine, at least in part, the host and tissue specificities of certain virus infections. It has been postulated that Hepatitis B virus (HBV) has binding sites for polymerized human serum albumin serves as an agent for the specific introduction of HBV into human hepatocytes.
It would therefore be desirable to provide vaccines which involve the determinant sites essential to the infectious properties of the virus. Furthermore, the viral proteins or particles may be used for antibody production for use in diagnostic assays and treatment.
2. Description of the Prior Art
Machida et al., Gastroenterology (1983) 85:268-274 has disclosed evidence suggesting the existence of polyalbumin receptors on Hepatitis B surface antigen (HBsAg). See also, Machida, et al., ibid. (1984) 86:910-918). The receptor was indicated as a polypeptide of 31 kilodaltons (kd), found in low amounts in serum derived HBsAg particles (Stibbe and Gerlich, J. Virol. (1983) 46:626-628. The entire genome of HBV has been cloned in E. coli and its nucleotide sequence determined (Valenzuela et al., Nature (1979) 280:815-819; Valenzuela et al., Animal Virus Genetics (1980) pp 57-70). Hepatitis B surface antigen particles have been synthesized and assembled in S. cerevisiae, Valenzuela et al., Nature (1982) 298:374-350. Binding of human serum polyalbumin to HBV in HBsAg particles has been reviewed by Thung and Gerber, Liver (1981) 1:75-80. Neurath, et al., Science (1984) 224:392-394 describes the 55 amino acids of the pre-surface (pre-S) region as containing a new dominant epitope. Michel, et al., Int. Symp. on Viral Hepatitis, 1984, describes the synthesis of the pre-S-sAg particle in chinese hamster ovary cells using a SV40-dihydrofolatereductase vector.